Tumor stem cells (TSCs) are the only subpopulation of a heterogeneous mixture of tumor cells that have the capacity to regenerate tumors in vivo. Tumor stem cells are also are characterized by their capacity for self-renewal, and differentiation into the myriad other types of cells typically found in malignant tumors. Like ordinary cells, the TSC phenotype is controlled by a unique gene expression program. However, the regulatory mechanisms that control TSC gene expression leading to malignant tumor initiation and proliferation are unclear. A better understanding of the regulatory mechanisms that govern TSC gene expression and contribute to the TSC identity would be of considerable scientific and practical interest.